Sodium Carbonate → 6-(2-methyl-4-pyridinyl)-2-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-1,2,4-triazine-3,5(2H,4H)-dione

Participants

Reaction Conditions

Reaction Steps

6-bromo-2-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-1,2,4-triazine-3,5(2H,4H)-dione (P8,100 mg, 0.218 mmol) was suspended in a degassed mixture of 1,2-Dimethoxyethane (DME) (3.629 mL)/Water (0.726 mL), then 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (143 mg, 0.653 mmol), SODIUM CARBONATE (69.2 mg, 0.653 mmol), 2-biphenylyl(dicyclohexyl)phosphane (15.26 mg, 0.044 mmol) and Tetrakis (50.3 mg, 0.044 mmol) were added. The mixture was then heated at 90° C. and stirred at that temperature for 3 hours. The reaction mixture was then cooled down to room temperature, 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (143 mg, 0.653 mmol), 2-biphenylyl(dicyclohexyl)phosphane (15.26 mg, 0.044 mmol), SODIUM CARBONATE (69.2 mg, 0.653 mmol) and Tetrakis (50.3 mg, 0.044 mmol) were added again, the mixture was stirred at 90° C. for further 2 hours, then left stirring at room temperature overnight. The mixture was concentrated under reduced pressure and partitioned between AcOEt and water. Phases were separated, organic phase was dried over sodium sulphate and concentrated under reduced pressure. The residue was purified by Preparative HPLC affording 6-(2-methyl-4-pyridinyl)-2-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-1,2,4-triazine-3,5(2H,4H)-dione (E3, 15.7 mg, 0.033 mmol, 15.29% yield).

Provenance & Evidence